Studies on the mechanism of 3,5,3'-triiodothyronine-induced suppression of secretagogue-induced thyrotropin release in vitro.
A double column perifusion procedure was used to study the feedback inhibition of L-T3 on TSH secretion from rat anterior pituitary fragments. Matching pituitary halves were pretreated with T3 (10(-7) M) for 2 h before exposure to 10(-8) M TRH, 59 mM K+, or 5 mM Ba2+ . TRH, high K+, and Ba2+ resulted in a 2-fold or greater stimulation of TSH release. T3 significantly inhibited the stimulation by these secretagogues to 0.77, 0.78, and 0.52 of control for TRH, high K+, and Ba2+, respectively. Neither rT3 (10(-7) M) nor T3 added together with TRH had an effect on TSH release by this secretagogue. Perifusion with 3.5 x 10(-5) M cycloheximide or 10(-6) M actinomycin D 1 h before and during T3 administration led to greater TSH release with TRH than in the presence of T3 alone. Neither protein synthetic inhibitor increased TRH responsiveness of pituitary fragments when perifused alone. When cycloheximide was perifused in a similar protocol before high K+ or Ba2+, there again was a significant decrease in the T3-induced inhibition of TSH release by these secretagogues. Cycloheximide alone did not increase TSH release in response to high K+ or Ba2+, eliminating this as a possible explanation for the enhanced TSH response when antibiotic was present with T3. These results indicate that the in vitro effect of T3 on secretagogue-induced TSH release can be blocked by an inhibitor of protein synthesis. The inhibitory effect of T3 on high K+- and Ba2+-induced TSH release suggests that the site of the acute T3 inhibition of TSH release may be subsequent to TRH interaction with its receptor.
D000818:Animals; D001464:Barium / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D008297:Male; D010477:Perfusion / Q000379:methods; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*; D014285:Triiodothyronine, Reverse / Q000494:pharmacology
D014284:Triiodothyronine; D003609:Dactinomycin; D001464:Barium; D014285:Triiodothyronine, Reverse; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D003513:Cycloheximide; D011188:Potassium